A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

旋磁场对胆结石病人胆汁中胆红素、钙、胆固醇和pH的影响

目的 探讨旋磁场与大面积静磁场对置对胆结石病人胆汁中总胆红素（BIT）、直接胆红素（BID）、间接胆红素（BII）、钙（Ca）、胆固醇（CH）和pH的影响。方法 旋磁组30例,测定旋磁处理前后65对胆汁样本。空白对照组15例,留取前后30对胆汁样本。将直径12mm圆形稀土永磁片110块,表面磁感应强度210mT,分别间隔10mm贴于210mm×220mm铁皮上形成一个大面积磁板与旋磁头表面静磁感应强度160mT,旋转平均表面磁感应强度100mT呈异名极对置,磁板置肝区背侧,旋磁头置剑突下处理40min。结果 旋磁组胆结石病人胆汁（n=65）:经旋磁场与磁板对置处理前减去处理后差值的x±s和t值分别为BIT41.81±93.52、3.59;BID 13.57±43.70、2.46;BII28.27±61.67、3.32;Ca 0.19±0.31、4.87;CH0.12±0.29、3.36;pH 0.01±0.27、0.30。除pH外,其余各项指标P值均<0.05。对照组胆汁（n=30）:间隔时间前后差值的x±s和t值分别为BIT4.42±22.05、1.14;BID2.40±12.37、1.06;BII2.52±46.27、0.30;Ca0.01±0.18、0.50;CH0.03±0.15、0.94;pH 0.009±0.06、0.84。P值均>0.05。结论 在本项磁场类型、强度和时间处理条件下,旋磁场与磁板对置能明显影响胆结石病人胆汁中的BIT、BID、BII、Ca和CH的浓度变化,且有显著降低的作用。     

Single-dose oral omeprazole for reduction of gastric residual acidity in adults for outpatient surgery

Omeprazole is a substituted benzimidazole that causes dose-dependent intracellular inhibition of gastric acid secretion in humans. This double-blind study examined the effect of omeprazole in decreasing gastric acidity and gastric residual volume in outpatient adults. Unpremedicated outpatients, ASA I-III, 18 years or older (n = 17), were randomly assigned to receive omeprazole 80 mg, or placebo by mouth the night before scheduled elective outpatient surgery. The patients were fasted for 8 h prior to surgery. After the patient was anesthetized, an orogastric tube was inserted with proper placement verified by auscultation for gastric sounds. Gastric residual contents were withdrawn into a Luken's trap, and pH was then determined and gastric volume indexed to weight (ml.kg-1). Data were analyzed by a t-test, with P less than 0.05 considered statistically significant. Patient characteristics of both groups were similar. There was a statistically significant difference between the two groups for pH (P = 0.02), but not between the two groups for gastric volume indexed to weight (P = 0.07).     

Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate

Summary Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00–06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24 h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00–06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.     

前列腺按摩液pH测定在慢性前列腺炎中的临床应用价值

Ⅲ型前列腺炎，即慢性非细菌性前列腺炎/慢性盆底疼痛综合征(CP/CPPS)在各型前列腺炎中发病率最高、争议最多且疗效最不确定，按前列腺按摩液中白细胞数量，又分为炎症性(ⅢA)和非炎症性(ⅢB)两个亚型。但研究表明，白细胞数与症状程度不相关，提示除白细胞和细菌的因素外，还有其他引起CPPS症状的因素存在，     

Gastroesophageal reflux disease (GERD), extraesophageal reflux (EER) and recurrent chronic rhinosinusitis

Chronic polypoid rhinosinusitis (CRS) is a common disease, affecting approximately 16% of the adult population in the US every year. In addition to many well known predisposing factors, an association with reflux disease is hypothesized. Such an association might explain the recurrence of polyposis in the face of improved surgical techniques and postsurgical treatment of CRS. At present it is unclear whether extraesophageal reflux directly injures the sinus mucosa, whether gastroesophageal reflux leads to vagus-mediated neuroinflammatory changes, or whether both mechanisms occur separately or simultaneously. In patients suffering from recurrent CRS (n=20) and healthy volunteers (n=20), ambulatory 24 h two channel pH testing was performed. The number of reflux events, the fraction of the total time during which pH was below 4, and the reflux area index (RAI) were determined in the esophagus as well as in the hypopharynx. Patients with recurrent CRS had significantly more reflux events in the esophagus and the fraction of pH<4 and the RAI were increased up to 10-fold compared to healthy volunteers. In contrast to the esophagus, these differences were not observed in the hypopharynx. Recurrent CRS is often associated with GERD but not with EER. Recurrent disease or prolonged recovery after surgery should raise the suspicion of reflux disease as a possible triggering factor. Because GERD itself cannot be diagnosed by laryngoscopy, and because of the subjectivity of symptoms such as heartburn, the otolaryngologist should consider double-probe pH testing as the diagnostic procedure of choice.     

Viscoelastic properties of acid- and alkaline-treated human dermis: a correlation between total surface charge and elastic modulus

BACKGROUND: One of the major mechanical functions of collagenous tissues is the storage, transmission and dissipation of elastic energy during mechanical deformation. In skin, mechanical energy is stored during loading and then is transmitted and dissipated, which protects skin from mechanical failure. Thus energy storage (elastic properties) and dissipation (viscous properties) are important characteristics of extracellular matrices. METHODS: A uniaxial incremental stress relaxation test method has been used to characterize the time-dependent (viscous) and time-independent (elastic) properties of human dermis. Viscoelasticity was investigated in processed human dermis that was equilibrated at pHs of 3.0, 7.4 and 11.0 in an effort to study the link between electrostatic interactions within the collagen matrix and macroscopic tissue properties. RESULTS: Our results show that the solution pH and the charge on collagen significantly affected the high-strain elastic behavior of dermis; the elastic behavior of skin has previously been shown to be directly correlated with axial stretching of the collagen triple helix in crosslinked collagen fibrils. A positive linear correlation existed between the high-strain elastic modulus and both pH (R(2)=0.96) and the total number of charged residues on collagen (R(2)=0.93). These results provide in vitro/ex vivo evidence that charged groups on the surface of collagen molecules in processed human skin influence the high-strain elastic properties of dermis and are likely to be involved in elastic energy storage. CONCLUSION: It is proposed that the pH and charged residue dependency of the elastic modulus suggests that charged pair interactions and repulsions within and between collagen molecules are involved in elastic energy storage during stretching at high strains. It is hypothesized that elastic energy storage is associated with the stretching of pairs of charged amino acid residues that are found primarily in the flexible regions of collagen molecules.     

The pH of Exhaled Breath Condensate of Patients with Allograft Rejection After Lung Transplantation

Endogenous airway acidification, as assessed by the condensate pH, has been implicated in the pathophysiology of inflammatory airway diseases such as cystic fibrosis and asthma. The aim of this study was to investigate the pH of condensate in patients after lung transplantation (LTX). From the cohort of transplanted patients at our center, 83 patients (9 heart-lung transplantation, 48 double-lung transplantation, 26 single-lung transplantation) were recruited and analyzed in a cross-sectional manner: 26 patients were diagnosed with chronic rejection or bronchiolitis obliterans syndrome (BOS), 7 patients were diagnosed with acute rejection (AR) while 50 patients had no evidence of rejection according to the International Society for Heart and Lung Transplantation criteria. The condensate pH was significantly reduced in patients with BOS and AR when compared to patients without rejection and control subjects (5.8 +/- 0.5 and 6.2 +/- 0.4 versus 6.6 +/- 0.4 and 6.5 +/- 0 .4, respectively; p < 0.05). Moreover, there was a significant correlation between condensate pH levels and the BOS grade (r =-0.62; p < 0.01), the FEV(1) (r = 0.39; p < 0.01) and the total cell and neutrophil count in bronchoalveolar lavage fluid (r =-0.39 and r =-0.56, respectively; p < 0.01). Airway acidification occurs in BOS and may directly or indirectly reflect airway inflammation in patients with allograft rejection after LTX. Measuring condensate pH might thus be a new tool for the evaluation of rejection in lung transplant patients.     

不同微生物诱导家蝇幼虫表达抗菌肽的特性

研究不同微生物诱导家蝇幼虫表达的抗菌肽特性.用3种不同的病源菌通过针刺感染的方法诱导家蝇幼虫表达抗菌肽,通过Sephadex G25分离,用Hult mark改进法和抑菌圈测定法作抑菌试验,用毛细管电泳（CE）分析不同微生物诱导得到的抗菌肽样品差异,检测抗菌肽的热稳定性和酸碱耐受性.发现不同微生物诱导产生的家蝇抗菌肽具有广谱抑菌性,但不同样品对不同病源菌抑菌活性有差异,不同测定抑菌效果的方法对抑菌结果有影响,各种抗菌肽样品CE蛋白谱具有明显不同.抗菌肽样品都具有热稳定性和酸碱耐受性.说明不同微生物诱导产生的家蝇抗菌肽类型以及抗菌肽含量与诱导源有关,抗菌肽为家蝇幼虫体内固有成分,诱导增加了抗菌肽的表达量同时刺激新抗菌肽的产生.用志贺氏菌、金黄色葡萄球菌、鼠伤寒沙门氏菌诱导家蝇幼虫可产生较多含量高活性好的抗菌肽.